Previous studies have demonstrated that immune checkpoint inhibitors (ICIs) increase the risk of endocrine-related adverse effects; however, how these risk estimates change with longer durations of follow-up remains unclear. This study aimed to evaluate whether the risks of various endocrine-related adverse effects vary across different follow-up durations among cancer patients receiving chemotherapy with or without ICI therapy.

We identified 1,049,548 cancer patients who received chemotherapy without ICIs and 62,266 cancer patients who received chemotherapy with ICIs between January 1, 2013 to December 31, 2024 from the TriNetX global electronic health record network. After excluding individuals with pre-existing endocrine disorders and performing 1:1 propensity score matching, the final study cohort included 62,266 ICI-treated patients (ICI group) and 62,266 chemotherapy-only patients (non-ICI group). We assessed the risks of new-onset adrenal insufficiency (ICD-10: E27.1–E27.4), hypothyroidism (ICD-10: E03.2, E03.8, E03.9), hyperthyroidism (ICD-10: E05, E06), and type 1 diabetes mellitus (T1D) (ICD-10: E10) at 1, 3, 5, 7, and 9 years, as well as across total follow-up duration, using Cox proportional hazards regression models.

The mean age of the study cohort was 62.3 ± 13 years, with men (54.5%) and White patients (63.8%) comprising the majority. During the first year of follow-up, the ICI group exhibited markedly increased risks of adrenal insufficiency (Hazard Ratio [HR] 8.70; 95% Confidence Interval [CI] 5.56–13.57), hypothyroidism (HR 4.67; 95% CI 3.88–5.62), and hyperthyroidism (HR 6.36; 95% CI 4.19–9.65), while the risk of T1D did not differ significantly between groups. By the third and fifth years of follow-up, the risk of adrenal insufficiency peaked (HR 9.03), whereas the risks of hypothyroidism and hyperthyroidism declined compared to the first year. The risk of T1D became apparent beginning in the third year, with HRs consistently around 2.5–2.7 throughout later follow-up. At the end of the observation period, the ICI group continued to show significantly increased risks of all endocrine-related adverse outcomes relative to the non-ICI group.

Compared with the non-ICI group, patients receiving ICIs demonstrated significantly increased risks of adrenal insufficiency, hypothyroidism, hyperthyroidism, and T1D; however, the magnitude of these risks varied by follow-up duration. Clinicians should be aware of these time-dependent risk patterns, and continuous endocrine monitoring is warranted throughout the entire follow-up period for patients treated with ICIs.